This proposal is a request for a competitive renewal of our Program Project. The next phase of this ongoing research will address the mechanisms which affect heterogeneity in the lung. The previous program dealt with the mechanisms of, and compensations for, restrictions to flow through the pulmonary circulation. The first focus was on causes of pulmonary blood flow restriction. There were studies of mechanisms of ademd formation, hypoxic pulmonary vasoconstriction and thrornbotic obstruction. The second focus was on cornpensations for pulmonary blood flow restriction, particularly the role of the bronchial circulation, and the systernic response to a raised right heart pressure. Building on this,.the focus of the present program is on the mechanisms of heterogeneity of ventilation and perfusion in the lung. Seven projects and three cores are proposed which address both intraregional and interregional mechanisms of heterogeneity. The projects deal either with ventilation or perfusion separately, the matching of the two as it affects gas exchange and influences on edema formation. The approach is multidisciplinary, with investigators trained in medicine, physiology, anesthesiology, bioengineering, morphology, engineering and radiology. It is a result of two decades of interest in pulmonary physiology and medicine and .collaboration between the investigators. The program is designed to support other research, particularly in ARDS and pulmonary vascular disease, which is proceeding at this institution. The strengths of the proposal include the integration of many disciplines, the productivity of this group of investigators and the adoption of new experimental approaches using imaging, morphological reconstruction and fractal evaluation of heterogeneity.